In 2045, Luna is colonized and the New Horizons Lunar Colony is created. In 2514, the Unitologist extremist group, the Circle (led by Jacob Danik) attacks Luna's colony. They succeed in their endeavor to "free" the planet's Marker from the Earth Government-facilitated shroud and to kill Isaac Clarke for his actions in the Titan Station. Their actions result in a Necromorph outbreak which presumably wipes out the New Horizons colony.
After the outbreak, Isaac Clarke and Sgt. John Carver return to Earth and Luna in the CMS Terra Nova recovered from above Tau Volantis. They attempt to contact anyone on the radio channels on Earth and Luna, however all they receive is people being slaughtered by Necromorphs. They later find the Brethren Moons have arrived at Earth and are attempting to exterminate the human race. Terra Nova then starts crashing into the Moon.