In addition to circulating haemocytes, the immune system of the solitary ascidianCiona robustarelies on two organs, the pharynx and the gut, and encompasses a wide array of immune and stress-related genes. How the pharynx and the gut ofC. robustareact and adapt to environmental stress was assessed upon short or long exposure to hypoxia/starvation in the absence or in the presence of polystyrene nanoplastics. We show that the immune response to stress is very different between the two organs, suggesting an organ-specific immune adaptation to the environmental changes. Notably, the presence of nanoplastics appears to alter the gene modulation induced by hypoxia/starvation in both organs, resulting in a partial increase in gene up-regulation in the pharynx and a less evident response to stress in the gut. We have also assessed whether the hypoxia/starvation stress could induce innate memory, measured as gene expression in response to a subsequent challenge with the bacterial agent LPS. Exposure to stress one week before challenge induced a substantial change in the response to LPS, with a general decrease of gene expression in the pharynx and a strong increase in the gut. Co-exposure with nanoplastics only partially modulated the stress-induced memory response to LPS, without substantially changing the stress-dependent gene expression profile in either organ. Overall, the presence of nanoplastics in the marine environment seems able to decrease the immune response ofC. robustato stressful conditions, hypothetically implying a reduced capacity to adapt to environmental changes, but only partially affects the stress-dependent induction of innate memory and subsequent responses to infectious challenges.