QPX is a protistan parasite that infects the hard clam, Mercenaria mercenaria, often leading to the development of inflammatory masses (nodules) that result from intensive hemocyte infiltration to the infection site in an attempt to encapsulate and neutralize parasite cells. Inside nodules, active host-pathogen interactions take place leading either to the death of the parasite or invasion of surrounding tissues, infection worsening and in many cases host death. This presentation will summarize our findings on host-parasite interactions using a complementary set of high-throughput genomic, transcriptomic and proteomic methods. Transcriptomic profiling of nodule tissues and parasite cultures allowed the identification of QPX transcripts produced in clams during infection. In parallel, the investigations allowed the identification of host factors and molecular pathways potentially involved in clam response to the infection. Proteomic methods allowed the identification of host plasma factors that recognize and bind parasite cells in vitro. These included prominent pattern recognition receptors (PRR) such as complement c1q-domain containing proteins and lectins. Results further showed that these PRR are induced upon infection. Finally, RADSeq methods contrasting allele frequencies between naïve clams and clams that survived QPX epizootics allowed the identification of genetic markers (SNPs) associated with disease resistance. These markers are being validated via selective breeding trials. Altogether, these results provide valuable information on the molecular crosstalk between QPX and its clam host and open the way for “precision breeding” approaches to improve aquaculture production and protect natural resources.