Dose-specific reprogramming of the mucociliary-humoral immune interface in oysters upon biodegradable microplastics...

Poly(lactic acid) microplastics (PLA-MPs) have been widely regarded as alternatives to conventional plastics, but their cellular effects on marine filter-feeders remain poorly understood. In this study, single-cell RNA sequencing (scRNA-seq) was used to resolve the early gill responses of Hong Kong oyster (Crassostrea hongkongensis) after 7 days of UV-aged PLA-MPs exposure at two different concentrations. PLA exposure triggered significant dose remodeling along the mucus-cilia-humoral immune particle processing pathway, among which the humoral immune characterized by mature soluble recognition functions displayed the highest sensitivity, acting as the potential early response indicators for the PLA-MPs. At the low dose, mucous cells first initiated transcriptional reprogramming related to physicochemical regulation, whereas ciliated cells showed a decoupled motility-directionality. Meanwhile, the mature humoral recognition gate weakened, and the residual immunes state shifted to local coating and containment. At the high dose, mucous cells exhibited higher oxidative metabolism and glycoprotein processing demands. Motile and polar-related ciliary states decreased, while junction remodeling states accumulated and formed a maturation bottleneck in ciliated cells. Humoral immunity further shifted from mature recognition to proteolytic regulation. Cell-cell communication suggested dose specific reorganization of homology supported signaling networks, with ionocyte-associated interactions more prominent at the low dose and sensory epithelium and junctional barrier interactions more prominent at the high dose; these predicted interactions require further functional validation. Taken together, these findings defined a nonlinear transition from low-dose physicochemical interface adaptation to high-dose particle burden associated mucociliary-immune remodeling, providing a cellular and mechanistic basis for identifying early biological effects and assessing the ecological risks of biodegradable microplastics in estuarine bivalves.