Freshwater shortages and the growing demand for sustainable aquaculture have highlighted the potential of euryhaline species for brackish water and estuarine aquaculture. Asian clam (Corbicula fluminea) serves as a commercially valuable bivalve in East Asia. However, the physiological and molecular mechanisms underlying their salinity adaptation remain poorly understood. In this study, we investigated the transcriptomic and cellular responses of two Asian clam populations (estuarine and freshwater) exposed to salinities of 0, 15, and 25 PSU for 12 h, 24 h, and 5 days. A total of 50 RNA-Seq libraries (25 per population) were generated, revealing population-specific transcriptional reprogramming. The estuarine population exhibited a more tightly regulated and pathway-specific response, particularly under prolonged high-salinity exposure, with significant enrichment in MAPK and NF-κB signaling, amino acid metabolism, and osmoregulatory processes. In contrast, the freshwater population showed a broader yet less targeted transcriptomic profile. Weighted gene co-expression network analysis (WGCNA) identified key gene modules and hub genes associated with salinity stress, highlighting divergent regulatory strategies between populations. Histological and ultrastructural analyses of gill tissues corroborated transcriptomic findings, revealing more severe tissue damage in the freshwater population under high salinity, whereas the estuarine population maintained structural integrity. These results provide comprehensive insights into the molecular basis of salinity adaptation in Asian clam, offering valuable guidance for selective breeding programs aimed at enhancing salinity tolerance, expanding aquaculture potential, and improving environmental resilience in Asian clam.
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