After Saturday's 2-1 win over Prescot Cables, Liddle's side went in search of a fourth match unbeaten, but were undone by two close range finishes on a mild November night at the Towbar Express Stadium.
The Seasiders started well, with Hartlepool United loanee Campbell Darcy involved in the first chance of the evening. The defender broke into the area before flashing the ball across the face of goal, but both Connor Simpson and Stephen Walker were unable to get a touch.
There were moments of danger for Town early on - Preston thumped an effort over the bar from distance and Howe called Shane Bland into action with an effort from a tight angle.
Liddle's side retained a threat in the final third, with Walker striking into the hands of Dylan Wharton after cutting inside onto his left foot. These warning signs for Gainsborough continued into the second half too, as Darcy also found the gloves of Wharton.
But on the hour mark, they fell behind. It was a disappointing opener to concede from the Seasiders' point of view, with Joe Stacey able to run through the defence before picking out Preston at the back post who couldn't miss, resultantly giving his side the lead.
Liddle, working with a squad depleted due to injuries and illness, made a change after falling behind with Nathan Thomas coming on in place of Darcy but Town continued to find themselves on the back foot.
After a let-off from Ashley Jackson who struck the woodwork, Howe wasn't so forgiving when he lashed home into the top corner to give his side a 2-0 lead. Again, the manner of the goal will have disappointed the Seasiders.
Walker, looking a tired figure, forced some defensive work from Gainsborough in the 80th minute as Whitby looked to mount a late charge to muster an unlikely comeback. After charging forwards, the former Middlesbrough forward was prevented from scoring by a defensive block.
However, it was always Gainsborough who looked more likely to score the next goal if there were to be one, with Aaron Simpson making Bland save with his feet, and Stacey seeing the ball nicked off his toes by the retreat Connor Smith.
But the damage was already done as Town suffered a first league defeat since September.