The invasion of the parasitic copepod Mytilicola intestinalis represents an ideal tool to study host-parasite co-evolution in nature. From its source the parasite spread southwest towards the island of Texel (the Netherlands) and north towards the island of Sylt (Germany), forming two invasion fronts that cover a similar time span. In a cross-infection experiment, we infected blue mussel hosts from Texel, Sylt and Kiel, where the parasite is absent, with parasites from Texel and Sylt, to form sympatric, allopatric and naïve infestation combinations, respectively. On the phenotypic level we found that hosts in the Wadden Sea had different evolutionary trajectories: hosts on Texel evolved resistance while hosts on Sylt evolved tolerance. To identify the underlying molecular mechanisms, we sequenced the transcriptomes from the different experimental combinations (sympatric, allopatric, no sympatry) and try to establish links to phenotypic differentiation.