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

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 <i>Sinonovacula constricta</i> 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 (<i>HIF-1α</i>) (to limit glycolytic acidosis) was followed by a chronic induction of <i>HIF-2α</i>, alongside the specific upregulation of the mitochondrial respiratory gene cytochrome c oxidase-6b (<i>COX-6b</i>). 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 (<i>ARG</i>) for detoxification, while nitric oxide synthase (<i>NOS</i>) 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 <i>S. constricta</i> navigates the bioenergetic conflict between detoxification and oxygen limitation, providing molecular targets for breeding stress-resistant aquaculture strains.