Low oxygen zones in coastal and open ocean ecosystems have expanded in recent decades, a trend that will accelerate with climatic warming. There is growing recognition that low oxygen regions of the ocean are also acidified, a condition that will intensify with rising levels of atmospheric CO2. Presently, however, the concurrent effects of low oxygen and acidification on marine organisms are largely unknown, as most prior studies of marine hypoxia have not considered pH levels. We experimentally assessed the consequences of hypoxic and acidified water for early life stage bivalves (bay scallops, Argopecten irradians, and hard clams, Mercenaria mercenaria), marine organisms of significant economic and ecological value and sensitive to climate change. In larval scallops, experimental and naturally-occurring acidification (pH, total scale  = 7.4–7.6) reduced survivorship (by >50%), low oxygen (30–50 µM) inhibited growth and metamorphosis (by >50%), and the two stressors combined produced additively negative outcomes. In early life stage clams, however, hypoxic waters led to 30% higher mortality, while acidified waters significantly reduced growth (by 60%). Later stage clams were resistant to hypoxia or acidification separately but experienced significantly (40%) reduced growth rates when exposed to both conditions simultaneously. Collectively, these findings demonstrate that the consequences of low oxygen and acidification for early life stage bivalves, and likely other marine organisms, are more severe than would be predicted by either individual stressor and thus must be considered together when assessing how ocean animals respond to these conditions both today and under future climate change scenarios.

Table S1. Seawater chemistry for first Menidia beryllina acidification and hypoxia experiment. Mean and standard deviation for temperature (°C), pH (total scale), dissolved oxygen (mg l-1), pCO 2 (µatm), total alkalinity (µmol kg-1), CO 3 2-(µmol kg-1), and total dissolved inorganic carbon (µmol kg-1).

Global ocean change threatens marine life, yet a mechanistic understanding of how organisms are affected by specific stressors is poorly understood. Here, we identify and compare the unique and common transcriptomic responses of an organism experiencing widespread fisheries declines, Argopecten irradians (bay scallop) exposed to multiple stressors including high p CO 2 , elevated temperature, and two species of harmful algae, Cochlodinium (aka Margalefidinium ) polykrikoides and Aureococcus anophagefferens using high‐throughput sequencing (RNA‐seq). After 48 hr of exposure, scallop transcriptomes revealed distinct expression profiles with larvae exposed to harmful algae ( C. polykrikoides and A. anophagefferens ) displaying broader responses in terms of significantly and differentially expressed (DE) transcripts (44,922 and 4,973; respectively) than larvae exposed to low pH or elevated temperature (559 and 467; respectively). Patterns of expression between larvae exposed to each harmful algal treatment were, however, strikingly different with larvae exposed to A. anophagefferens displaying large, significant declines in the expression of transcripts ( n = 3,615; 87% of DE transcripts) whereas exposure to C. polykrikoides increased the abundance of transcripts, more than all other treatments combined ( n = 43,668; 97% of DE transcripts). Larvae exposed to each stressor up‐regulated a common set of 21 genes associated with protein synthesis, cellular metabolism, shell growth, and membrane transport. Larvae exposed to C. polykrikoides displayed large increases in antioxidant‐associated transcripts, whereas acidification‐exposed larvae increased abundance of transcripts associated with shell formation. After 10 days of exposure, each harmful algae caused declines in survival that were significantly greater than all other treatments. Collectively, this study reveals the common and unique transcriptional responses of bivalve larvae to stressors that promote population declines within coastal zones, providing insight into the means by which they promote mortality as well as traits possessed by bay scallops that enable potential resistance.

15In most animals, respiratory activity inversely correlates with environmental oxygen 16 levels 1,2 . However, less is known about how the underlying neural circuitry encodes 17 oxygen information and modifies behaviours. Here, we characterize the oxygen sensing 18 circuit and reveal sensory coding principles in a Danio rerio larva, an optically 19 accessible vertebrate that increases respiration and startle-related responses under 20 hypoxia 3 . We observe that cranial sensory neurons receive input from multiple oxygen-21 sensing neuroendocrine cells, and then relay this information to hindbrain targets. 22Moreover, hypoxia evoked increase in cranial sensory dendrite calcium events indicates 23 an oxygen-driven change in input dimensionality, which is also represented in their 24 cytoplasm. Additionally, we estimate that a neural code using cytoplasmic calcium 25 events requires most of the cranial sensory neurons, whereas one integrating input 26 dimensionality needs only a third. Furthermore, we show that purinergic signalling at 27 the neuroendocrine cell-sensory neuron synapses drives hypoxia-induced respiratory 28 changes, independent of serotonin, which triggers startle-related responses. Collectively 29 we demonstrate that oxygen coding employs a "many-to-one" sensory circuit that 30 transforms ambient oxygen into neuronal activity and input dimensionality changes to 31 impact behaviour. More broadly, we suggest that multi-dimensional coding might be a 32 common feature of many-to-one circuit motifs, revealing a function for related circuits 33 across species. 34 35Mammals have evolved specialized neural circuitry to detect and respond to oxygen 36 changes. Neuroendocrine glomus cells in the carotid body sense blood oxygen levels and 37 communicate this information to the carotid sinus nerve, a branch of the glossopharyngeal 38 nerve, and the brainstem 4 . Typically, hypoxia is thought to depolarize glomus cells, which in 39 turn release ATP and acetylcholine 5 activating the carotid sinus nerve resulting in higher 40 respiratory rates 6,7 . In parallel, hypoxia also acts via serotonin and brainstem respiratory 41 circuits to promote arousal 8,9 . While neural circuitry and neurotransmitters driving hypoxia-42 induced responses have been described, how the cranial sensory neurons encode oxygen 43 levels and initiate changes in respiratory behaviours. To gain insights into the neuronal 44 dynamics, we probed these pathways in the transparent zebrafish larva. Teleost fish use both 45 the glossopharyngeal and vagal cranial sensory neurons to sense hypoxia 10 . In zebrafish, 46 these neurons innervate the gill-localized neuroendocrine cells (NECs), potential oxygen 47