Accumulation and depuration of ciguatoxins in green-lipped mussels fed toxic Gambierdiscus polynesiensis: Evidence from controlled feeding and transcriptomic analysis

(day 21, Experiment 2), with the majority of CTXs observed in the digestive system. Despite ongoing feeding for 10 more days, CTXs concentrations decreased until the end of the experiment, suggesting saturation and/or metabolic transformation. During a 35-day depuration period with CTX-free diet, mussels fully depurated CTXs (estimated initial rate of 0.90 µg kg⁻¹ day⁻¹). Parallel transcriptome analyses demonstrated that molecular responses lagged toxin accumulation: by day 19, mussels upregulated genes involved in endoplasmic reticulum stress (e.g., PDIA3), proteasomal degradation (e.g., PSMCs), autophagy (e.g., cathepsins), stress resistance (e.g., heat shock proteins) and innate immunity (e.g., MYD88). These coordinated responses suggest that transcriptional defence is activated once CTX load reaches a threshold or time. CTXs concentrations above safety thresholds and late onset of detoxification suggest that mussels may remain toxic for weeks after exposure. This study represents the first integrative assessment of CTXs accumulation, depuration and molecular stress responses, laying the groundwork for the use of molecular biomarkers to track exposure and improve harvest management in CTX-prone regions.