Disease causes significant coral mortality worldwide; however, factors responsible for intraspecific variation in disease resistance remain unclear. We exposed fragments of eight Acropora millepora colonies (genotypes) to putatively pathogenic bacteria (Vibrio spp.). Genotypes varied from zero to >90% mortality, with bacterial challenge increasing average mortality rates 4–6 fold and shifting the microbiome in favor of stress-associated taxa. Constitutive immunity and subsequent immune and transcriptomic responses to the challenge were more prominent in high-mortality individuals, whereas low-mortality corals remained largely unaffected and maintained expression signatures of a healthier condition (i.e., did not launch a large stress response). Our results suggest that lesions appeared due to changes in the coral pathobiome (multiple bacterial species associated with disease) and general health deterioration after the biotic disturbance, rather than the direct activity of any specific pathogen. If diseases in nature arise because of weaknesses in holobiont physiology, instead of the virulence of any single etiological agent, environmental stressors compromising coral condition might play a larger role in disease outbreaks than is currently thought. To facilitate the diagnosis of compromised individuals, we developed and independently cross-validated a biomarker assay to predict mortality based on genes whose expression in asymptomatic individuals coincides with mortality rates.

Understanding the drivers of intraspecific variation in susceptibility is essential to manage increasingly frequent coral disease outbreaks. We challenged replicate fragments of eight Acropora millepora genotypes with Vibrio spp. to quantify variation in lesion development and to identify host and coral-associated microbial community properties associated with resistance. While Vibrio spp. remained relatively rare in the microbiome of challenged corals, other stress-associated microbial taxa significantly increased in abundance. Contrary to expectations, higher constitutive immunity and more active immune responses did not confer higher resistance to bacterial challenge. Furthermore, more pronounced gene expression responses to bacterial challenge were associated with higher rather than lower mortality. A newly developed gene expression assay based on two genes related to inflammation and immune responses, deleted in malignant brain tumors 1 and a matrix metalloproteinase, predicted mortality under Vibrio treatment both in the initial experiment and in a validation experiment involving another 20 A. millepora genotypes. Instead of mounting more robust responses, resistant corals were largely unaffected by the bacterial challenge and maintained gene expression signatures of healthier condition, including elevated fluorescent proteins and ribosomal biosynthesis along with diminished ubiquitination. Overall, our results support the view that coral disease and mortality is commonly due to opportunistic pathogens exploiting physiologically compromised hosts rather than specific infections, and show, contrary to the prevailing wisdom, that greater immune responses do not necessarily translate into greater disease resistance.