RT journal article T1 The Ghrelin Analog GHRP-6, Delivered Through Aquafeeds, Modulates the Endocrine and Immune Responses of Sparus aurata Following IFA Treatment A1 Rodríguez Viera, Leandro A1 Caderno Peña, Anyell A1 Martinez, R. A1 Martínez Rodríguez, G. A1 Oliva Ramírez, Milagrosa A1 Perera, Erick A1 Mancera Romero, Juan Miguel A1 Martos Sitcha, Juan Antonio A2 Biología K1 peptide-based immunomodulators K1 growth hormone secretagogue K1 humoral immune response K1 dietary supplement K1 gilthead sea bream AB 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 Sparus aurata 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 il10, il15, il34, and mx1, indicating mucosal immune activation. In the spleen, GHRP-6-fed fish increased il8, il10, and ighm 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 S. aurata and suggest a protective effect on the fish’s immune system in this species. PB Multidisciplinary Digital Publishing Institute (MDPI) SN 2079-7737 YR 2025 FD 2025-07 LK http://hdl.handle.net/10498/37863 UL http://hdl.handle.net/10498/37863 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 21-sep-2026