Synergistic Effects of Ammonia and Hypoxia Stress on the Transcriptomic Responses of the Razor Clam (Sinonovacula...

The co-occurrence of ammonia nitrogen and hypoxia represents a physiologically taxing synergistic challenge for benthic bivalves-as it forces a conflict between the high energy demand for detoxification and the limited energy supply under low oxygen, yet the tissue-specific strategies underlying their resilience remain poorly understood. This study investigated the physiological and transcriptomic responses of the razor clam Sinonovacula constricta to ammonia (AG), hypoxia (HG), and their combination (HAG) over 96 h. Transcriptomic profiling revealed that the gill and hepatopancreas employ distinct, organ-coordinated adaptive strategies rather than a uniform systemic response. The gill prioritized respiratory homeostasis by fine-tuning oxygen sensing: transcriptional suppression of hypoxia-inducible factor 1-α (HIF-1α) (to limit glycolytic acidosis) was followed by a chronic induction of HIF-2α, alongside the specific upregulation of the mitochondrial respiratory gene cytochrome c oxidase-6b (COX-6b). In contrast, the hepatopancreas executed a critical metabolic trade-off centered on arginine metabolism. Under combined stress, arginine flux was redirected toward the urea cycle via a robust upregulation of arginase (ARG) for detoxification, while nitric oxide synthase (NOS) was concurrently suppressed. This reciprocal regulation suggests a strategy to prioritize ammonia clearance and energy conservation at the expense of immune signaling. These findings elucidate how S. constricta navigates the bioenergetic conflict between detoxification and oxygen limitation, providing molecular targets for breeding stress-resistant aquaculture strains.