Oyster cellular architecture and innate immune programs resolved by single-cell RNA sequencing

Barrier mucosal tissues in marine invertebrates coordinate filtration, gas exchange, and frontline innate immunity, yet their cellular organization and division of functions remain poorly resolved. This study generated a tissue-resolved single-cell atlas in a marine invertebrate Crassostrea hongkongensis, defining twenty cell types. The framework revealed a diversified phagocyte lineage composed by five phagocytic cells with three terminal strategies: rapid extracellular containment, deep intracellular clearance, and a resolution program that couples degradation with matrix restoration. We also identified three humoral immune populations with complementary recognition and effector roles that collaborated with phagocytes and epithelial cells. Barrier epithelium supports acted as organizers rather than redundant producers of soluble effectors, and shaped immune activity through defined communication and adhesion programs that coordinated proliferation, survival, and migration. A neural-related compartment comprised of neural progenitor-like, neuron-like, and neuroendocrine cells, and exhibited predominantly sender roles toward epithelial and immune targets consistent with transmitter and peptide-mediated control of ciliary flow, secretory activity, as well as the priming of phagocytic and humoral effectors. Ligand receptor inference highlighted adhesion modules centering on neural cell adhesion molecule (NCAM) and the receptor type protein tyrosine phosphatase (PTPRM) as the key pathways of communication between neural, epithelial, and immune populations. Our finding present a compact taxonomy to map immune programs with precise cellular contexts, and further our understanding of resilience and health in variable coastal environments. © 2026 Elsevier Ltd