Abstract

Microplastic pollution, particularly from polyethylene (PE), poses an increasing threat to coastal ecosystems, yet how particle size and exposure duration jointly regulate organismal responses remains poorly understood. Here, we investigated the size- and time-dependent toxic effects of PE-MPs (10 μm and 50 μm) on the Kumamoto oyster ( Crassostrea sikamea ) using an integrative framework combining physiological biomarkers (SOD, CAT, MDA), histopathology (gills and hepatopancreas), transcriptomics (gills), and metabolomics (hepatopancreas) during acute (1 day), short-term (7 days), and long-term (14 days) phases. Both PE-MP sizes induced significant oxidative stress and tissue injury in a time-dependent manner, with smaller particles casing more persistent oxidative stress, greater metabolic disturbance, and stronger immune suppression. Multi-omics analyses revealed a clear phase-dependent response pattern characterized by early defense activation, short-term metabolic reprogramming, and long-term functional suppression. Acute exposure activated oxidative stress responses, cytoskeletal remodeling, and particle clearance–related pathways, whereas short-term exposure was associated with metabolic reprogramming characterized by enhanced glycolysis and amino acid metabolism, suggesting increased energetic demands during stress responses. In contrast, long-term exposure resulted in coordinated suppression of immune, digestive, and lipid metabolic-related pathways, together with a metabolic shift toward long-term energy conservation. Overall, these findings suggest that PE-MPs exposure may induce coordinated physiological and metabolic adjustments associated with energy trade-offs under chronic stress conditions, highlighting the importance of particle size and exposure duration in ecological risk assessment for coastal and aquaculture environments.