Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution

The Egyptian fruit bat displays tolerance to lethal viruses and unique dietary adaptations, but the molecular basis for this is not fully understood. To this end, we generated detailed maps of bat gut, lung and blood cells using spatial and single-cell transcriptomics. We compared bat with mouse and human cells to reveal transcriptional divergence in genetic programs associated with environmental interactions and immune responses. Complement system genes are transcriptionally divergent, uniquely expressed in both bat lung and gut epithelium, and undergo rapid coding-sequence evolution across bat species. We further identify lack of expression of genes related to specific nutrient absorption in bat top villus enterocytes, along with expression of evolutionarily young genes. Profiling of PBMCs, challenged with immune stimuli, discovered a monocyte subset with conserved interferon expression between species, suggesting strong regulatory constraints to avoid an excessive immune response. Our study thus uncovers conserved and divergent innate immune pathways in Egyptian fruit bat tissues, providing a unique resource to study bat immunity and evolution. ### Competing Interest Statement The authors have declared no competing interest.