Bats are asymptomatic reservoir hosts for several highly pathogenic viruses. Understanding this enigmatic relationship between bats and emerging zoonotic viruses requires tools and approaches which enable the comparative study of bat immune cell populations and their functions. We show that bat genomes have a conservation of immune marker genes which delineate phagocyte populations in humans, while lacking key mouse surface markers such as Ly6C and Ly6G. Crossreactive antibodies against CD44, CD11b, CD14, MHC II, and CD206 were multiplexed to characterize circulating monocytes, granulocytes, bone-marrow derived macrophages (BMDMs) and lung alveolar macrophages (AMs) in the cave nectar bat Eonycteris spelaea. Transcriptional profiling of bat monocytes and BMDMs identified additional markers-including MARCO, CD68, CD163, CD172α, and CD88which can be used to further characterize bat myeloid populations. Bat cells often resembled their human counterparts when comparing immune parameters that are divergent between humans and mice, such as the expression patterns of certain immune cell markers. A genome-wide comparison of immune-related genes also revealed a much closer phylogenetic relationship between bats and humans compared to rodents. taken together, this study provides a set of tools and a comparative framework which will be important for unravelling viral disease tolerance mechanisms in bats. Bats, belonging to the order Chiroptera, are the only mammals capable of powered flight. In the mammalian tree, Chiropterans are placed within the super-order Laurasiatheria and their close extant relatives include the carnivores and ungulates 1. Phylogenetic analysis has further classified bats into two suborders-the Yinpterochiroptera which encompass the non-echolocating Old-world fruit bats and one microbat lineage (Rhinolophidae), and the Yangochiroptera which includes the rest of the echolocating microbats 1,2. The cave nectar bat Eonycteris spelaea utilized in this study is a pteropodid bat within the Yinpterochiroptera lineage, and has a broad geographical distribution across South and South East Asia 3. Bats are key ecosystem service providers, acting as pollinators, dispersing fruits and seeds, and controlling insects of agricultural and public health importance 4. Bat species from both suborders are also reservoir hosts to a wide range of highly lethal zoonotic viruses with pathogenic potential in both humans and livestock 5,6. Hence there is a significant interest in understanding the unique host biology responsible for the ability of bats to harbor pathogenic viruses asymptomatically 7. A prevailing theory for the coexistence of bats and viruses is that adapting to physiological stressors associated with the evolution of powered flight necessitated a re-balancing of the chiropteran immune system, with consequent effects on viral disease tolerance and infection-associated immunopathology. In line with this hypothesis, several intracellular sensors capable of detecting endogenously derived danger signals have a re...