Integrated biochemical, histological, and transcriptomic analyses reveal dose-dependent effects of sodium alginate on the physiology of Meretrix meretrix.

Natural polysaccharides are increasingly explored as functional additives in aquaculture, yet their safe and effective dose windows remain poorly defined in bivalves. Here, we evaluated the dose-dependent effects of sodium alginate ( 0, 10, and 20 mg/L) on the hard clam Meretrix meretrix over a 60-day culture period by integrating growth performance, antioxidant indices, intestinal histology, and hepatopancreas transcriptomics. SA10 consistently produced superior growth, and quadratic regression based on weight gain rate predicted an optimal concentration of 11.14 mg/L. Although SA20 maintained partial growth benefits at later stages, it induced marked intestinal lesions (shortened/disordered villi and impaired goblet cells) and oxidative damage, evidenced by a significant increase in malondialdehyde despite elevated SOD, CAT, and GSH-Px activities. RNA-seq revealed extensive transcriptional remodeling under SA20, identifying 985 DEGs (SA0 vs. SA20) and 728 DEGs (SA10 vs. SA20), with 218 shared core-responsive genes. Enrichment analyses highlighted coordinated regulation of pathways involved in cellular catabolism and redox homeostasis (lysosome, autophagy, phagosome, AMPK signaling, and glutathione metabolism) together with apoptosis-related processes. Notably, apoptosis-associated genes showed an overall suppression pattern (e.g., downregulation of pro-apoptotic caspases) alongside upregulation of inhibitors of apoptosis, suggesting a compensatory survival strategy under high-dose exposure. Collectively, these findings define an effective SA range that supports growth while indicating intestinal and oxidative-stress risks at elevated concentrations, providing a basis for dose optimization in clam aquaculture.