Amoebic Gill Disease (AGD), caused by the protozoan extracellular parasite Paramoeba perurans, is a disease affecting Atlantic salmon (Salmo salar) aquaculture. Many studies to date have investigated the pathogenesis of ADG focusing on the host immune response in the gill after the appearance of clinical symptoms. This study investigated the gill transcriptomic profile of pre-clinical AGD using RNA-sequencing (RNA-seq) technology. RNA-seq libraries generated at 4, 7, 14 and 16 days post inoculation (dpi) identified 29,357 Differentially Expressed Genes (DEGs). RNA-seq data was validated using real-time, quantitative PCR (qPCR) analysis of 10 selected immune genes. DEGs mapped to 224 Gene Ontology (GO) terms, 27 reference pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and 15 Reactome Gene Sets. Immune suppression was evident at 7 dpi, prior to there being any evidence of ADG on the gill, involving signalling pathways for interleukins, Nod-like receptors, B-cell and T-cell receptors, and the differentiation of Th1/Th2 and Th17 cells. The results of this study suggest a mechanism for how N. perurans circumvents the host immune response to establish a successful infection, and could potentially lead to the development of novel strategies for AGD mitigation or prevention in aquaculture.