The Ghrelin Analog GHRP-6, Delivered Through Aquafeeds, Modulates the Endocrine and Immune Responses of Sparus aurata Following IFA Treatment

The aquaculture industry has experienced considerable growth in recent decades, stimulating research into sustainable and functional feed formulations, mainly related to using high-quality, safe, and environmentally friendly feed ingredients. The employment of immunomodulatory additives is a promising strategy to enhance fish health and performance. In this study, the effects of the ghrelin analog GHRP-6 peptide included in the diet (500 µg/kg of feed) on the endocrine and immune responses of <i>Sparus aurata</i> following Incomplete Freund's adjuvant (IFA) treatment were assessed. After 97 days, fish were intraperitoneally injected with 100 µL of saline solution or IFA/100 g fish and sampled 72 h post-injection. Our results indicated that fish fed GHRP-6 maintained stable plasma levels of lactate, triglycerides, and cortisol after IFA treatment, in contrast to control-fed fish, which showed significant metabolic stress. Circulating immunoglobulin levels enhanced significantly in the GHRP-6/IFA group, suggesting a stimulated humoral immune response. Transcriptomics analysis revealed that the anterior intestine was the most responsive tissue, with upregulation of <i>il10</i>, <i>il15</i>, <i>il34</i>, and <i>mx1</i>, indicating mucosal immune activation. In the spleen, GHRP-6-fed fish increased <i>il8</i>, <i>il10</i>, and <i>ighm</i> expression, highlighting a balanced pro- and anti-inflammatory response and support for adaptive immunity. Multivariate analysis confirmed that dietary GHRP-6 modulates immune gene expression in a tissue- and stimulus-specific manner, without inducing histological alterations in the intestine or spleen. Taken together, these preliminary results indicate that this peptide is a viable and safe dietary supplement to improve immune resilience and increase the production efficiency of <i>S. aurata</i> and suggest a protective effect on the fish's immune system in this species.