The gill ectoparasite Sparicotyle chrysophrii is considered the most threatening pathogen in gilthead seabream (Sparus aurata), one of the main cultured species in the Mediterranean. The objective of the present study was to profile the gill microbiota along a S. chrysophrii infection and to study the local (gills) and systemic (liver and spleen) transcriptomic response in a high-intensity infection to unravel local and systemic routes and interactions and have a deeper understanding of this host-microbiota-parasite system.